Our overall objective is to develop chemotherapeutic tools for the treatment of herpes simplex. We will continue our study of arabinosylthymine (araT) and related compounds that act in a similar manner (i.e., phosphorylated by herpesviral deoxythymidine kinase (dTK) but not by mammalian cytosol dTK). We will synthesize several nucleosides not previously tested for activity with the herpesviral dTKs, determine their ability to serve as substrates for the viral dTKs, as well as their activity against herpesviruses in cell culture and, if indicated, in animals. At the same time we will determine their activity against growing uninfected cells in culture. The modifications proposed are aimed at providing pyrimidine nucleoside analogs that by virtue of their increased ability to serve as substrates for the herpes simlex virus type 2 dTK will show an increased selectivity for HSV-2. Finally we will complete our studies of the metabolism of araT and 5-methyl araC (an intracellular araT donor) by using radioactive compounds in control and herpesvirus-infected hamsters and localizing the sites of viral DNA synthesis and drug action (in particular deamination of 5 methyl araC to araT) by autoradiography.